Generation of Pmel-dependent conditional and inducible Cre-driver mouse line for melanocytic-targeted gene manipulation.

Conditional and inducible gene targeting using Cre/loxP-mediated recombination is a powerful reverse genetics approach used to study spatiotemporal gene functions in specified cell types. To enable temporal gene manipulation in the melanocyte lineage, we established a novel inducible Cre-driver mouse line by targeting an all-in-one tetracycline/doxycycline (Dox)-inducible Cre expression cassette into the Pmel locus (Pmel ), a gene locus preferentially expressed in pigment cells. By crossing these Cre-driver mice with a strong Cre-reporter mouse line, Gt(ROSA)26Sor , we show the effectiveness of the Pmel mouse line in facilitating Dox-inducible Cre/loxP recombination in a wide variety of pigment cell lineages including hair follicle melanocytes and their stem cells.

A DISC1 point mutation promotes oligomerization and impairs information processing in a mouse model of schizophrenia.

Disrupted-in-schizophrenia 1 (DISC1) is strongly associated with schizophrenia, but it remains elusive how the modification of the intermolecular interaction of DISC1 affects the information processing in brain. We show that a DISC1 point mutation alters intermolecular cohesiveness promoting the phase separation, and disrupts sensorimotor gating monitored by the prepulse inhibition in a mouse model of schizophrenia. Although the conformation of DISC1 partial peptide with the schizophrenia-related mutation L607F in human or the corresponding L604F in mouse was essentially indistinguishable from the wild type (WT) as long as monitored by fluorescence, circular dichroism, ultracentrifugation, dynamic light scattering and nuclear magnetic resonance, the atomic force microscopy was able to detect their morphological distinctions.